Mark C Eisler

Sleeping sickness in Uganda: a thin line between two fatal diseases

Abstract Objective To determine, through the use of molecular diagnostic tools, whether the two species of parasite that cause human African trypanosomiasis have become sympatric. Design Blood sampling of all available patients between June 2001 and June 2005 in central Uganda and between July and September 2003 in northwest Uganda and analysis of subcounty sleeping sickness records in Uganda between 1985 and 2005. Setting Sleeping sickness treatment centres in central and northwest Uganda and in south Sudan. Participants Patients presenting at the treatment centres and diagnosed as having sleeping sickness. Main outcome measure Classification of parasites from patients from each disease focus as either Trypanosoma brucei rhodesiense (acute form) or T b gambiense (chronic form). Results Blood from 231 patients with sleeping sickness in central Uganda and from 91 patients with sleeping sickness in northwest Uganda and south Sudan were screened for T b rhodesiense (detection of SRA gene) and T b gambiense (detection of TgsGP gene). All samples from central Uganda were classified as T b rhodesiense, and all samples from northwest Uganda and south Sudan were identified as T b gambiense. Conclusions The two focuses of human African trypanosomiasis remain discrete, but the area of Uganda affected by the acute form of human sleeping sickness has increased 2.5-fold since 1985, spreading to three new districts within the past five years through movement of infected livestock. Without preventive action targeted at the livestock reservoir of this zoonotic disease, it is likely that the two disease focuses will converge. This will have a major impact on diagnosis and treatment of this neglected disease. Real time monitoring is recommended, using molecular diagnostic tools (at a regional surveillance centre, for example) targeted at both livestock and human patients.

African bovine trypanosomiasis: the problem of drug resistance

The three trypanocides used to control tsetse-transmitted trypanosomiasis in domestic animals in Africa have been in use for over 40 years and, not surprisingly, resistance of trypanosomes to these drugs has emerged. Because of the relatively limited market in Africa and the high costs of developing and licensing new drugs, international pharmaceutical companies have shown little interest in the development of new trypanocides for use in either animals or humans. Therefore, the current challenge is to achieve optimal use of the relatively old existing drugs, and it is in this context that the problem of drug resistance has to be quantified--as discussed here by Stanny Geerts, Peter Holmes, Oumar Diall and Mark Eisler.

Neglected and endemic zoonoses

Endemic zoonoses are found throughout the developing world, wherever people live in close proximity to their animals, affecting not only the health of poor people but often also their livelihoods through the health of their livestock. Unlike newly emerging zoonoses that attract the attention of the developed world, these endemic zoonoses are by comparison neglected. This is, in part, a consequence of under-reporting, resulting in underestimation of their global burden, which in turn artificially downgrades their importance in the eyes of administrators and funding agencies. The development of cheap and effective vaccines is no guarantee that these endemic diseases will be eliminated in the near future. However, simply increasing awareness about their causes and how they may be prevented—often with very simple technologies—could reduce the incidence of many endemic zoonoses. Sustainable control of zoonoses is reliant on surveillance, but, as with other public-sector animal health services, this is rarely implemented in the developing world, not least because of the lack of sufficiently cheap diagnostics. Public–private partnerships have already provided advocacy for human disease control and could be equally effective in addressing endemic zoonoses.

The diagnosis of trypanosome infections: applications of novel technology for reducing disease risk

Reliable DNA based methodologies to determine prevalence of trypanosome species in domestic livestock have been available for over 10 years. Despite this, they are rarely used to generate baseline data for control operations for these diseases in the field. Rather, such operations tend to rely on data which can be generated using low technology methods such as direct observation of parasites by light microscopy. Here we show the pitfalls of relying on such low tech methodology which, although simple in its application, can provide inaccurate and inadequate data on which to base control methodologies. Our analysis of 61 cattle selected for trypanosome carrier status by either microscopy, low PCV or poor condition score, showed that 90% were infected with trypanosomes while 84% of the total were infected with T. brucei. Diagnosis by PCR on buffy coat preparations on Whatman® FTA® matrices was the most sensitive methodology relative to the gold standard, whereas microscopy was the least sensitive. n(African Journal of Biotechnology: 2002 1(2): 39-45)

Standardised tests in mice and cattle for the detection of drug resistance in tsetse-transmitted trypanosomes of African domestic cattle

Resistance to the drugs used to control African animal trypanosomosis is increasingly recognised as a constraint to livestock production in sub-Saharan Africa. The most commonly used tests for detection of trypanocidal drug resistance are tests using mice or ruminants, but these suffer from lack of standardisation and hence it may be difficult to compare the results of different investigators. Tests in mice are less expensive than tests in ruminants, but while tests in mice they may be useful as a general guide to resistance in a geographic area they should not be extrapolated to cattle on an individual trypanosome level. Moreover, the commonly used protocols are too laborious for their application to large number of trypanosome isolates on an area-wide basis. This paper presents guidelines for standardised testing of trypanocidal drugs in vivo, and introduces a simplified single-dose test for use in mice, which is convenient for use in areas with limited laboratory facilities. The single-dose test is appropriate for characterisation of geographic areas in terms of trypanocidal drug resistance using large numbers of trypanosome isolates, for making comparisons between areas, and for monitoring changes in trypanocidal drug resistance over time. Multiple-dose tests may be used to determine the degree of resistance of individual stabilates to be determined precisely in mice are also described, but for logistical reasons these will rarely be conducted on more than a few stabilates, and testing of a larger number of stabilates in the single-dose test will generally provide more useful information. Finally, we describe tests in cattle that may be used to determine the efficacy of recommended curative doses of trypanocidal drugs for the treatment of infection with individual trypanosome isolates, including Trypanosoma vivax, which is rarely infective for mice.

Integrated control of vector-borne diseases of livestock – pyrethroids: panacea or poison?

Tick- and tsetse-borne diseases cost Africa approximately US

Characterisation of the wildlife reservoir community for human and animal trypanosomiasis in the Luangwa Valley, Zambia.

4-5 billion per year in livestock production-associated losses. The use of pyrethroid-treated cattle to control ticks and tsetse promises to be an increasingly important tool to counter this loss. However, uncontrolled use of this technology might lead to environmental damage, acaricide resistance in tick populations and a possible exacerbation of tick-borne diseases. Recent research to identify, quantify and to develop strategies to avoid these effects are highlighted.

Human brucellosis in urban and peri-urban areas of Kampala, Uganda.

Background Animal and human trypanosomiasis are constraints to both animal and human health in Sub-Saharan Africa, but there is little recent evidence as to how these parasites circulate in wild hosts in natural ecosystems. The Luangwa Valley in Zambia supports high densities of tsetse flies (Glossina species) and is recognised as an historical sleeping sickness focus. The objective of this study was to characterise the nature of the reservoir community for trypanosomiasis in the absence of influence from domesticated hosts. Methodology/Principal Findings A cross-sectional survey of trypanosome prevalence in wildlife hosts was conducted in the Luangwa Valley from 2005 to 2007. Samples were collected from 418 animals and were examined for the presence of Trypanosoma brucei s.l., T. b. rhodesiense, Trypanosoma congolense and Trypanosoma vivax using molecular diagnostic techniques. The overall prevalence of infection in all species was 13.9% (95% confidence interval [CI]: 10.71–17.57%). Infection was significantly more likely to be detected in waterbuck (Kobus ellipsiprymnus) (Odds ratio [OR]u200a=u200a10.5, 95% CI: 2.36–46.71), lion (Panthera leo) (ORu200a=u200a5.3, 95% CI: 1.40–19.69), greater kudu (Tragelaphus strepsiceros) (ORu200a=u200a4.7, 95% CI: 1.41–15.41) and bushbuck (Tragelaphus scriptus) (ORu200a=u200a4.5, 95% CI: 1.51–13.56). Bushbucks are important hosts for T. brucei s.l. while the Bovidae appear the most important for T. congolense. The epidemiology of T. vivax was less clear, but parasites were detected most frequently in waterbuck. Human infective T. b. rhodesiense were identified for the first time in African buffalo (Syncerus caffer) and T. brucei s.l. in leopard (Panthera pardus). Variation in infection rates was demonstrated at species level rather than at family or sub-family level. A number of significant risk factors interact to influence infection rates in wildlife including taxonomy, habitat and blood meal preference. Conclusion and Significance Trypanosoma parasites circulate within a wide and diverse host community in this bio-diverse ecosystem. Consistent land use patterns over the last century have resulted in epidemiological stability, but this may be threatened by the recent influx of people and domesticated livestock into the mid-Luangwa Valley.

Herd prevalence of bovine brucellosis and analysis of risk factors in cattle in urban and peri-urban areas of the Kampala economic zone, Uganda

A retrospective case–control study of human brucellosis in urban, peri‐urban, and rural areas in Kampala, Uganda was undertaken to find the risks associated with the disease using the medical records of Mulago National Referral Hospital (Mulago Hospital). From the Brucella agglutination test (BAT) records between June 2004 and May 2006, 652 positive results were found. The case–control study showed that living in urban areas was a risk factor for brucellosis. The numbers of improved and cross‐breed cattle per 1000 households were calculated on the basis of data obtained from interviews of 75 randomly selected local councils (LCls) in an area between 5 and 20 km radii from the city center of Kampala. Cattle‐keeping activities were, however, unpopular in urban areas compared to peri‐urban and rural areas. Poor correlation between the distribution of human brucellosis cases and the distribution of cattle suggested that most of the brucellosis cases resulted from consumption of raw milk transported from peri‐urban and rural areas of Kampala and/or dairy production areas outside Kampala.

Local and plasma antibody responses to the parasitic larval stages of the abomasal nematode Ostertagia circumcincta

BackgroundHuman brucellosis has been found to be prevalent in the urban areas of Kampala, the capital city of Uganda. A cross-sectional study was designed to generate precise information on the prevalence of brucellosis in cattle and risk factors for the disease in its urban and peri-urban dairy farming systems.ResultsThe adjusted herd prevalence of brucellosis was 6.5% (11/177, 95% CI: 3.6%-10.0%) and the adjusted individual animal prevalence was 5.0% (21/423, 95% CI: 2.7% - 9.3%) based on diagnosis using commercial kits of the competitive enzyme-linked immunosorbent assay (CELISA) for Brucella abortus antibodies. Mean within-herd prevalence was found to be 25.9% (95% CI: 9.7% - 53.1%) and brucellosis prevalence in an infected herd ranged from 9.1% to 50%. A risk factor could not be identified at the animal level but two risk factors were identified at the herd level: large herd size and history of abortion. The mean number of milking cows in a free-grazing herd (5.0) was significantly larger than a herd with a movement restricted (1.7, p < 0.001).ConclusionsVaccination should be targeted at commercial large-scale farms with free-grazing farming to control brucellosis in cattle in and around Kampala city.